The purpose of this project is to determine whether proto-oncogenes are functional in human hematopoietic cells and whether these genes are involved in hematopoietic differentiation. The proto-oncogenes are homologous to viral oncogenes; indeed the viral oncogenes have been derived from their cellular homologues. Our studies have focused on the 5 q- syndrome, a refractory anemia characterized by decreased erythroid precursors and abnormal megakaryocytic differentiation. An interstitial deletion in the long arm of chromosome 5 is characteristically present in such patients. A cellular proto-oncogene (fms) has been localized near the deletion. Using a sensitive S1 nuclease analysis, we have shown that the fms mRNA is present in bone marrow cells. The protein encoded by the v-fms homologue to the cellular fms proto-oncogene has the characteristics of a membrane receptor. In our studies, we have shown-using monoclonal antibodies raised against the v-fms protein-that the c-fms protein is present on human bone marrow cells. The second facet of this project has focused on the status of the fms proto-oncogene in cells of patients with the 5 q- syndrome. Bone marrow cells from two of the patients have been fused to CHO cells. In appropriate selective medium, human chromosome 5 is retained in such cells because of the presence of the DHFR locus on this chromosome. Hybrids containing either the normal chromosome 5 or the chromosome 5 having the interstitial deletion have been obtained. In both patients the fms gene has been shown to be deleted from the abnormal chromosome. These data are most consistent with the hypothesis that the fms proto-oncogene encodes for a membrane receptor important for erythropoietic differentiation and that the hemizygosity that results from the 5 q- deletion effectively reduces receptor number leading to erythroid hypoplasia.